Perinatal iron deficiency decreases cytochrome oxidase activity in specific regions of neonatal rat brain

M. T. DeUngria, F. Rao, Monica M Luciana, Michael K Georgieff

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Brain iron deficiency bodes poorly for cognitive neurodevelopment in older infants and is present in newborns following gestations complicated by diabetes mellitus or intrauterine growth retardation. Cytochrome oxidase (CytOx) is an iron-containing enzyme involved in oxidative phosphorylation; its activity reflects neuronal metabolism. Regional CytOx activity has been mapped in the iron sufficient adult rat brain but not in iron sufficient or deficient neonates. We hypothesized that neonatal brain iron deficiency decreases CytOx activity and expected more pronounced differences in nuclei involved in cognition. Pregnant Sprague-Dawley rats were fed iron deficient or sufficient chow from GD 1 until PND 7. Cylox activity of 19 brain nuclei was measured histochemically utilizing diaminobenzidine on frozen 15μ thick coronal brain sections in 25 rats from each group. Quantitation of optical density as a measure of CytOx staining was by Image-1. Brain iron staining was homogeneously reduced with a mean of 86% (range: 75-100%) less overall staining in the iron deficient group (p<0.001). Overall CytOx staining was decreased by a mean of 23% in the iron deficient group (p<0.001) however CytOx activity loss in the iron deficient group was not homogeneous among nuclei (range: 0-42%). Areas with significantly reduced CytOx activity (p<0.001) included all subareas of the hippocampus (CA1: 42%, CA3ab: 34%, CA3c: 33%, and dentate gyrus: 32%), the piriform cortex (17%), the medial dorsal thalamic nucleus (28%), and the cingulate cortex (41%). The hippocampus is central to recognition memory circuits, the piriform cortex to working and spatial memory circuits and the cingulate cortex to emotional memory circuits. The medial dorsal thalamic nucleus acts as a relay station for cognitive memory information. In contrast the anterior thalamic nucleus, the lateral amygdaloid nucleus and the medial habenula, areas not involved in cognition, did not have significantly reduced CytOx activity (0%, 10%, and 16% respectively). We conclude that several areas of the brain involved in memory processing are vulnerable to perinatal iron deficiency as evidenced by decreased neuronal metabolic activity. This vulnerability may contribute to the poorer long-term developmental outcome observed among infants born following pregnancies complicated by gestational diabetes or intrauterine growth retardation.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Issue number2
StatePublished - Feb 1999


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